title: Hsp90 can accommodate the simultaneous binding of the FKBP52 and HOP proteins.
abstract: The regulation of steroidogenic hormone receptor-mediated activity plays an important role in the development of hormone-dependent cancers. For example, during prostate carcinogenesis, the regulatory function played by the androgen receptor is often converted from a growth suppressor to an oncogene thus promoting prostate cancer cell survival and eventual metastasis. Within the cytoplasm, steroid hormone receptor activity is regulated by the Hsp90 chaperone in conjunction with a series of co-chaperone proteins. Collectively, Hsp90 and its binding associates form a large heteromeric complex that scaffold the fully mature receptor for binding with the respective hormone. To date our understanding of the interactions between Hsp90 with the various TPR domain-containing co-chaperone proteins is limited due to a lack of available structural information. Here we present the stable formation of Hsp90(2)-FKBP52(1)- HOP(2) and Hsp90(2)-FKBP52(1)-p23(2)-HOP(2) complexes as detected by immunoprecipitation, time course dynamic light scattering and electron microscopy. The simultaneous binding of FKBP52 and HOP to the Hsp90 dimer provide direct evidence of a novel chaperone sub-complex that likely plays a transient role in the regulation of the fully mature steroid hormone receptor.
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W. University Ave, El Paso, Texas 79968, USA.
authors.forename: Zacariah L
authors.initials: ZL
authors.lastname: Hildenbrand
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Molugu
authors.forename: Nadia
authors.initials: N
authors.lastname: Herrera
authors.forename: Citlally
authors.initials: C
authors.lastname: Ramirez
authors.forename: Chuan
authors.initials: C
authors.lastname: Xiao
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Bernal
mesh_terms: D019281:Dimerization; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008027:Light; D011485:Protein Binding; D012542:Scattering, Radiation; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C476884:HOPX protein, human; D018841:HSP90 Heat-Shock Proteins; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4